Practice Essentials
Vanishing twin syndrome is the identification of a multifetal gestation with subsequent disappearance of one or more fetuses. The rate of multifetal gestation at conception is higher than the incidence noted at birth. [1] Vanishing twin syndrome has been diagnosed more frequently with the increased use of ultrasonography in early pregnancy. [2, 3]
Signs and symptoms
The most common presenting complaints include bleeding, uterine cramps, and pelvic pain.
See Presentation for more detail.
Diagnosis
Laboratory studies
Recent vanishing twin syndrome has been shown to increase levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG). Alpha-fetoprotein levels are also elevated compared with values at similar junctures in both a singleton pregnancy and a normal twin pregnancy. [4]
Imaging studies
Ultrasonography is used to confirm the diagnosis of early twin pregnancy. Follow-up ultrasonography reveals the pregnancy loss (vanishing twin).
See Workup for more detail.
Management
Uncomplicated vanishing twin syndrome requires no special medical care. If a fetus papyraceus remains, the pregnancy should be followed closely with serial ultrasonographic evaluation of the live fetus.
See Treatment for more detail.
Background
Vanishing twin syndrome was first described by Stoeckel in 1945. [1] In vitro fertilization techniques have improved the understanding of the syndrome because these pregnancies are closely monitored, and the number of implanted fertilized eggs is known. [5]
In vanishing twin syndrome, there may be complete reabsorption of a fetus, formation of a fetus papyraceus (ie, a "mummified" or compressed fetus), or development of a subtle abnormality on the placenta such as a cyst, subchorionic fibrin, or amorphous material. [6]
The cause of vanishing twin syndrome is frequently unknown; however, this condition occurs more often in fetuses with genetic or chromosomal abnormalities. [6] Improper cord implantation may also play a role in some cases.
The timing of this event significantly affects the outcome of the viable twin and the maternal complications. For example, if the event occurs during the second half of pregnancy, the fetus could develop cerebral palsy or cutis aplasia, and the mother could develop preterm labor, infection, puerperal hemorrhage, consumptive coagulopathy, or obstruction of labor. [7, 8]
Pathophysiology
Abnormalities that result in the disappearance of a fetus usually appear to be present from early in development rather than occurring from an acute insult. Placental or fetal analysis frequently reveals chromosome abnormalities. These abnormalities include diploidy, triploidy, and alternate sex chromosome results on placental pathology, skin biopsies, and chorionic villus sampling. [9, 10, 11, 12] Study findings of the viable twin chromosomes in these reports are normal. Therefore, it is thought that the vanished twin had a chromosomal abnormality resulting in disappearance.
Epidemiology
United States statistics
The frequency of multiple gestations is 3.3-5.4% at 8 weeks' gestation. [1] Vanishing twin syndrome occurs in 21-30% of multifetal gestations. [5]
International statistics
Research from a European series of pregnancies associated with assisted reproductive technology (ART) show that 10-15% of singleton births were initially twin gestations.
International prevalence is similar to that of the United States.
Race-, sex-, and age-related demographics
No predilection for any race has been reported.
No predilection for either sex has been reported in the vanishing twin.
Researchers report more cases in women older than 30 years. Advanced maternal age is also a recognized risk factor for fetal and placental chromosome abnormalities.
Prognosis
Morbidity/mortality
Maternal first-trimester morbidity
Morbidity when vanishing twin syndrome occurs during the first trimester is limited. The mother is most likely to develop mild vaginal bleeding and cramping. If the event occurs later in the first trimester, morbidity may be similar to that of the second and third trimesters.
Maternal morbidity in the second and third trimesters
Maternal complications include premature labor, infection from a retained fetus, severe puerperal hemorrhage, consumptive coagulopathy, and obstruction of labor by a low-lying fetus papyraceus causing dystocia and leading to a cesarean delivery. [7]
The diagnosis of vanishing twin in a pregnancy significantly increases both preterm (< 37 gestational weeks) and very preterm (< 32 gestational weeks) births. [7]
Fetal morbidity and mortality
In addition to loss of a twin, the surviving fetus has an increased risk of cerebral palsy, particularly if vanishing twin syndrome occurred during the second half of pregnancy. [13]
Other forms of morbidity reported in the surviving twin are aplasia cutis or areas of skin necrosis. In twins connected through vascular connection by placental anastomoses, temporary hypotension in the surviving twin at the time of fetal demise of the vanishing twin leads to poor perfusion and skin necrosis. [14]
Complications
Prematurity
Singleton pregnancies that were reduced to singleton because of vanishing twin syndrome are more likely to be delivered preterm (35.1 vs 38.2 wk, P =.0001). These rates of preterm delivery are similar to twin in vitro fertilization (IVF) pregnancies (23%). [15] In one series, singletons remaining after a vanishing twin event were associated with very premature birth (< 32 wk estimated gestational age). [16]
Low birth weight/small for gestational age
Singleton pregnancies that were reduced to singleton because of vanishing twin syndrome are at higher risk for growth restriction (32.6% vs 16.3% of control IVF singleton pregnancies). [17] Risks associated with intrauterine growth restriction include increased morbidity and mortality in the neonatal period and increased rates of hospitalization in the neonatal intensive care unit.
Cerebral palsy
Researchers proposed that vanishing twin syndrome could result in spastic cerebral palsy in the remaining twin. (Cerebral palsy is the most common hypothesized pathological clinical sequela in the viable twin.) [13]
A possible mechanism is the transfusion of thromboplastic proteins from the vanishing twin to the surviving twin, leading to disseminated intravascular coagulation (DIC). Researchers hypothesize that DIC results from reverse blood flow from the macerated twin to the viable twin, thus carrying thromboplastins into the circulation. This large thromboplastin load is hypothesized to lead to a state of DIC in the viable twin, which then leads to intrauterine central nervous system damage. [18]
Another proposed mechanism for central nervous system damage involves large amounts of blood loss from the surviving twin to the low resistance system of the vanishing twin through placental anastomoses. This transfusion could cause wide fluctuation in intravascular pressures, leading to intraventricular hemorrhage that results in cerebral palsy. [19]
Cerebral impairment in the survivor has also been linked to confirmed cases of vanishing twin with impairment on the Griffiths Mental and Developmental Scales and Optimality score (relative risk, 6.1; P=0.03). [19]
Associated congenital anomalies
A link in children with cerebral palsy and other congenital anomalies is possible. In one series, the relative risk for congenital malformations, including microcephaly, isolated hydrocephaly, eye, cleft lip/palate, and cardiac anomalies, increased over baseline from relative risk 3.1-116 (95% CI, 1.9-4.8 to 84 to 162.3; P< 0.01 to P< 0.0001) depending on the specific defect. [20] These anomalies are postulated to be due in part to perturbations in fetal flow in the surviving twin at the time of loss of the vanishing twin. [20]
Cutis aplasia
The mechanism of development of cutis aplasia is most likely vascular. There is thought to be decreased perfusion to the affected area at the time of demise of the vanished twin. Most case reports include a fetus papyraceous as the vanished twin. [14, 21]
Other complications
Preterm birth of the surviving twin has been described, with a 2.3-fold increased risk and a mortality rate that is 3-fold increased. [22, 23]
The surviving singleton infant after a twin vanishes has been shown to have a lower birth weight (mean difference, 368 g) than singleton pregnancies. [24]
Distinctive placental abnormalities, including an increased rate of small placentas (less than the 10th percentile by weight), have been identified in IVF pregnancies that involve a vanishing twin. [25]
